Neuropathy is one of the many complications of diabetes mellitus, along with micro- and macroangiopathy. Chronic sensorimotor distal symmetric polyneuropathy is the most common form between neuropathies; more than 30% of the diabetic patients are affected by this complication. Treatment is based on three cornerstones: (1) multifactorial intervention aimed at normoglycemia; (2) drugs that target pathogenic mechanisms and (3) symptomatic treatment. Among pathogenic treatments, alpha-lipoic acid and benfotiamine are available in several countries. Neuropathic pain, which affects 8-26% of diabetic patients, exerts a substantial impact on the quality of life. Among the centrally acting analgesic drugs, tricyclic antidepressants, carbamazepine, gabapentin and opioids have been mainly used to treat neuropathic pain. More recently, significant pain relief has been reported using agents such as duloxetine, a dual selective serotonin noradrenaline reuptake inhibitor, and pregabalin, an anticonvulsant, a specific modulator of the alpha2delta subunit of the voltage-dependent calcium channels. Until now, at least 50 new molecular entities have reached clinical stage of development. Strategies that may show promise over existing treatments include topical therapies, analgesic combinations and, in future, gene-related therapies.